Evaluation of potential inhibitors of squalene synthase based on virtual screening and in vitro studies.
Comput Biol Chem
; 80: 390-397, 2019 Jun.
Article
en En
| MEDLINE
| ID: mdl-31125877
ABSTRACT
Squalene synthase (SQS) is a potential target for hyperlipidemia treatment. To identify novel chemical scaffolds of SQS inhibitors, we generated 3D-QSAR pharmacophore models using HypoGen. The best quantitative pharmacophore model, Hypo 1, was selected for virtual screening using two chemical databases, Specs and Traditional Chinese Medicine database (TCM). The best-mapped hit compounds were then subjected to filtering by Lipinski's rule of five and docking studies to refine the hits. Finally, five compounds were selected from the top-ranked hit compounds for SQS inhibitory assay in vitro. Three of these compounds could inhibit SQS in vitro, and should be further evaluated pre-clinically as a treatment for hyperlipidemia.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Farnesil Difosfato Farnesil Transferasa
/
Inhibidores Enzimáticos
Tipo de estudio:
Diagnostic_studies
/
Screening_studies
Idioma:
En
Revista:
Comput Biol Chem
Asunto de la revista:
BIOLOGIA
/
INFORMATICA MEDICA
/
QUIMICA
Año:
2019
Tipo del documento:
Article